2. Academic Validation
  3. Discovery of novel 1,2,4-triazole schiff bases hybridized with 1,4-naphthoquinones as potent STAT3 inhibitors

Discovery of novel 1,2,4-triazole schiff bases hybridized with 1,4-naphthoquinones as potent STAT3 inhibitors

  • Bioorg Chem. 2025 Oct:165:108936. doi: 10.1016/j.bioorg.2025.108936.
Kai Yin 1,  Yujun Ruan 2,  Mingchen Guo 3,  Quanxin Tang 1,  Fayi Nie 4,  Yuwei Wang 1,  Hui Guo 1,  Ying Wang 1,  Sha Zhou 5,  Dezhen Yang 6,  Yuping Tang 1,  Ruyi Jin 7,  Hong Peng 8
Affiliations

Affiliations

  • 1 Shaanxi Key Lab Basic & New Herbal Medicament Research Center, College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, China.
  • 2 The Zhongzhou Laboratory for Integrative Biology, State Key Laboratory of Antiviral Drugs, School of Pharmacy, Henan University, Kaifeng, China.
  • 3 Xi'an Tie Yi High School, Xi'an, China.
  • 4 Shaanxi Key Laboratory of Acupuncture and Medicine, Shaanxi University of Chinese Medicine, Xianyang, China.
  • 5 State Key Laboratory of Elemento-Organic Chemistry, Institute of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering, College of Chemistry, Nankai University, Tianjin, China.
  • 6 Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, China.
  • 7 Shaanxi Key Lab Basic & New Herbal Medicament Research Center, College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, China. Electronic address: jinruyi@sntcm.edu.cn.
  • 8 Shenzhen Key Laboratory of Systems Medicine for Inflammatory Diseases, Shenzhen Campus of Sun Yat-sen University, Shenzhen, China. Electronic address: pengh37@mail.sysu.edu.cn.
PMID: 40907442 DOI: 10.1016/j.bioorg.2025.108936
Abstract

Signal transducer and activator of transcription 3 (STAT3) is closely related to a variety of cancers. The research of novel STAT3 inhibitors is an important and meaningful project for pharmaceutical chemist. In this study, 10 novel 1,4-naphthoquinones carrying 1,2,4-triazole derivatives were synthesized via a four-step synthesis starting from 2-hydroxynaphthalene-1,4-dione. The inhibitory activities of these compounds against four Cancer cells were tested at concentrations of 10, 1, 0.1 μM. The results exhibited that compound S1 showed outstanding anti-tumor activity. In addition, we tested the inhibitory curves of compound S1 on four types of cells, containing HeLa, HepG2, U87, LN229, with the IC50 values of 5.066 μM, 0.8089 μM, 1.970 μM, and 1.412 μM, respectively. Moreover, we verified the mechanism of S1 targeted to STAT3 through Western blot and qPCR experiments. Based on the good anti-tumor activity of S1 in cell level, we also tested the blood-brain barrier (BBB) crossing rate and the preliminary pharmacokinetic properties, and the result demonstrated S1 can cross the BBB. The above research indicated that compound S1 has excellent anti-tumor activity, which is worth for further study.

Keywords

1,2,4-triazole; 1,4-naphthoquinones derivatives; STAT3 inhibitors.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-178140
    STAT3 Inhibitor